Cytokine regulation of human microglial cell IL-8 production.
IL-8 involvement in neutrophil activation and chemotaxis may be important in inflammatory responses within the central nervous system, secondary to meningitis, encephalitis, and traumatic injury. The source of IL-8 within the brain during these inflammatory processes, however, is unknown. To explore the role of microglia in the production of IL-8, human fetal microglia, which are the resident macrophages of the brain, were treated with LPS and pro- and anti-inflammatory cytokines to determine their effects on IL-8 production. We found that IL-8 protein levels increased in response to LPS or IL-1 beta, or to TNF-alpha, which also corresponded to elevated IL-8 mRNA levels by RT-PCR. Pretreatment with IL-4, IL-10, or TGF-beta 1 potently inhibited the stimulatory effects of these proinflammatory agents. These findings indicate that human microglia synthesize IL-8 in response to proinflammatory stimuli, and that anti-inflammatory cytokines down-regulate the production of this chemokine. These results may have important therapeutic implications for certain central nervous system insults involving inflammation.
Ehrlich
L C
LC
Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, MN 55404, USA.
Hu
S
S
Sheng
W S
WS
Sutton
R L
RL
Rockswold
G L
GL
Peterson
P K
PK
Chao
C C
CC
D000367:Age Factors; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D005333:Fetus; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000276:immunology / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4